Yao et al. BMC Medical Genetics (2016) 17:49 DOI 10.1186/s12881-016-0307-1
CASE REPORT
Open Access
Breakpoints and deleted genes identification of ring chromosome 18 in a Chinese girl by whole-genome low-coverage sequencing: a case report study Hui Yao1†, Chuanchun Yang3†, Xiaoli Huang1, Luhong Yang1, Wei Zhao2,3, Dan Yin2,3, Yuan Qin1, Feng Mu2,3, Lin Liu2,3, Ping Tian1, Zhisheng Liu1 and Yun Yang2,3,4*
Abstract Background: Ring chromosome 18 [r(18)] is formed by 18p- and 18q- partial deletion and generates a ring chromosome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific phenotype, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion. The aim of this study is to identify the detailed breakpoints location and the deleted genes result from the r18. Case presentation: Here we describe a detailed diagnosis of a seven-year-old Chinese girl with a ring chromosome 18 mutation by a high-throughput whole-genome low-coverage sequencing approach without karyotyping and other cytogenetic analysis. This method revealed two fragment heterozygous deletions of 18p and 18q, and further localized the detailed breakpoint sites and fusion, as well as the deleted genes. Conclusions: To our knowledge, this is the first report of a ring chromosome 18 patient in China analyzed by wholegenome low-coverage sequencing approach. Detailed breakpoints location and deleted genes identification help to estimate the risk of the disease in the future. The data and analysis here demonstrated the feasibility of next-generation sequencing technologies for chromosome structure variation including ring chromosome in an efficient and cost effective way. Keywords: Ring chromosome, Whole-genome low-coverage sequencing, Detailed breakpoints, Detailed diagnosis
Background Ring chromosome 18 [r(18)] is formed from breakage of both ends of the chromosome and the break ends generate a ring chromosome [1]. Individuals with r(18) have 18p and 18q partial deletions and according phenotype, such as microcephaly, mental deficiency, hypotonia, and congenital heart defects [2, 3]. Short stature, microcephaly, mental deficiency, craniofacial dysmorphism and extremity abnormalities are the most commonly reported features in * Correspondence: @genomics.cn † Equal contributors 2 BGI-Wuhan, Wuhan 430075, China 3 BGI-Shenzhen, Shenzhen 518083, China Full list of author information is available at the end of the article
patients with r(18). The phenotype with r(18) syndrome is highly variable and depends on the combination of 18psyndrome and 18q- syndrome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific symptoms, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion [4]. Whole-genome low-coverage sequencing has been reported previously by our group to accurately detect chromosomal structural variation-associated breakpoints and affected region without cytogenetic analysis on patients [5]. In the current study, we applied whole-genome lowcoverage sequencing to characterize the ring chromosome 18 mutation at a molecular level in a Chinese young girl
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Yao et al. BMC Medical Genetics (2016) 17:49
Page 2 of 6
Fig. 1 Abnormalities of the craniofacial appearance. Facial appearance of the patient at age 7, showing flat midface, puffy eyelids, hypertelorism, epicanthic fold, flat nasal bridge, and micrognathia. a frontal view. b lateral view
for the first time. We described the full profile of clinical examination, genetic characterizations, and clinical treatment report. We localized the genomic breakpoints as well as identified the deleted genes. The deletion of the genes and detailed breakpoint identified help to understand the genotype- correlation and estimate the risk of the disease in the future.
Case presentation The patient was born to non-consanguineous at the year of 2006. The patient was born at 40 weeks gestation with a birth weight of 3,050 g and length of 49 cm. At 2 years of age, she was found shorter than children of the same age. In April 2008, she was diagnosed hypothyroidism in the local clinic. Replacement of thyroid hormone (levothyroxine) was started for the treatment of autoimmune hypothyroidism. Unregular treatment lasted one year and discontinue by parents themselves. At 6 and half years of age (March,2013), she came to our hospital for short stature. At the time of our first evaluation, she had a short stature problem (height: 90.7 cm [−6.0SD, equivalently 50 percentile of 2–2.5 years old], weight: 12.0 kg [
CASE REPORT
Open Access
Breakpoints and deleted genes identification of ring chromosome 18 in a Chinese girl by whole-genome low-coverage sequencing: a case report study Hui Yao1†, Chuanchun Yang3†, Xiaoli Huang1, Luhong Yang1, Wei Zhao2,3, Dan Yin2,3, Yuan Qin1, Feng Mu2,3, Lin Liu2,3, Ping Tian1, Zhisheng Liu1 and Yun Yang2,3,4*
Abstract Background: Ring chromosome 18 [r(18)] is formed by 18p- and 18q- partial deletion and generates a ring chromosome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific phenotype, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion. The aim of this study is to identify the detailed breakpoints location and the deleted genes result from the r18. Case presentation: Here we describe a detailed diagnosis of a seven-year-old Chinese girl with a ring chromosome 18 mutation by a high-throughput whole-genome low-coverage sequencing approach without karyotyping and other cytogenetic analysis. This method revealed two fragment heterozygous deletions of 18p and 18q, and further localized the detailed breakpoint sites and fusion, as well as the deleted genes. Conclusions: To our knowledge, this is the first report of a ring chromosome 18 patient in China analyzed by wholegenome low-coverage sequencing approach. Detailed breakpoints location and deleted genes identification help to estimate the risk of the disease in the future. The data and analysis here demonstrated the feasibility of next-generation sequencing technologies for chromosome structure variation including ring chromosome in an efficient and cost effective way. Keywords: Ring chromosome, Whole-genome low-coverage sequencing, Detailed breakpoints, Detailed diagnosis
Background Ring chromosome 18 [r(18)] is formed from breakage of both ends of the chromosome and the break ends generate a ring chromosome [1]. Individuals with r(18) have 18p and 18q partial deletions and according phenotype, such as microcephaly, mental deficiency, hypotonia, and congenital heart defects [2, 3]. Short stature, microcephaly, mental deficiency, craniofacial dysmorphism and extremity abnormalities are the most commonly reported features in * Correspondence: @genomics.cn † Equal contributors 2 BGI-Wuhan, Wuhan 430075, China 3 BGI-Shenzhen, Shenzhen 518083, China Full list of author information is available at the end of the article
patients with r(18). The phenotype with r(18) syndrome is highly variable and depends on the combination of 18psyndrome and 18q- syndrome. Loss of critical genes on each arm of chromosome 18 may contribute to the specific symptoms, and the clinical spectrum varieties may heavily depend on the extent of the genomic deletion [4]. Whole-genome low-coverage sequencing has been reported previously by our group to accurately detect chromosomal structural variation-associated breakpoints and affected region without cytogenetic analysis on patients [5]. In the current study, we applied whole-genome lowcoverage sequencing to characterize the ring chromosome 18 mutation at a molecular level in a Chinese young girl
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Yao et al. BMC Medical Genetics (2016) 17:49
Page 2 of 6
Fig. 1 Abnormalities of the craniofacial appearance. Facial appearance of the patient at age 7, showing flat midface, puffy eyelids, hypertelorism, epicanthic fold, flat nasal bridge, and micrognathia. a frontal view. b lateral view
for the first time. We described the full profile of clinical examination, genetic characterizations, and clinical treatment report. We localized the genomic breakpoints as well as identified the deleted genes. The deletion of the genes and detailed breakpoint identified help to understand the genotype- correlation and estimate the risk of the disease in the future.
Case presentation The patient was born to non-consanguineous at the year of 2006. The patient was born at 40 weeks gestation with a birth weight of 3,050 g and length of 49 cm. At 2 years of age, she was found shorter than children of the same age. In April 2008, she was diagnosed hypothyroidism in the local clinic. Replacement of thyroid hormone (levothyroxine) was started for the treatment of autoimmune hypothyroidism. Unregular treatment lasted one year and discontinue by parents themselves. At 6 and half years of age (March,2013), she came to our hospital for short stature. At the time of our first evaluation, she had a short stature problem (height: 90.7 cm [−6.0SD, equivalently 50 percentile of 2–2.5 years old], weight: 12.0 kg [
